Study provides further evidence for the effects of white matter fiber abnormalities and neuroinflammation on positive symptoms in patients with schizophrenia.

It's becoming evident that white matter fiber abnormalities, as well as aberrant immune system function, play a role in chronic neuropsychiatric disorders including schizophrenia. Individuals diagnosed with schizophrenia often present with positive symptoms such as delusions and hallucinations.

New findings published by NeuroImage Clinical provide further evidence for the association between delusions in patients with chronic schizophrenia and myelin abnormalities in the cingulum bundle. Data also point to an association between delusions and neuroinflammation or atrophy in the cingulum bundle.

Investigators used diffusion tensor MRI (DTI) to assess functional changes in diffusion anisotropy, and diffusion-tensor tractography (DTT) to examine the changes in the topical organization of white matter fiber structural network. According to the authors, current techniques don't allow for differentiation between changes in myelin and neuroinflammation, as both of these lead to a decrease in fractional anisotropy.

For this reason, investigators used a newly developed technique, free-water imaging, to distinguish between diffusion properties of white matter fibers and surrounding cerebrospinal fluid. “Neuroinflammation is associated with excessive extracellular free-water, which can be partialled out to yield improved DTI indices such as free-water corrected fractional anisotropy (FAT), free-water corrected radial diffusivity (RDT) and free-water corrected axial diffusivity (ADT), all of which provide a more precise estimation of tissue changes,” the authors wrote in their publication.

Researchers focused on the cingulum bundle, uncinate fasciculus, and fornix in 86 patients suffering with chronic schizophrenia [34 patients had state delusions (ie, delusions present during the past 30 days), 35 had a lifetime history but no delusions within the past 30 days, and 17 had never presented with delusions)]. These data were then compared with data collected from 28 typical, healthy control participants.

Data indicate that state and trait delusions in patients with schizophrenia are associated with microstructural changes such as myelin abnormalities in the cingulum bundle, as evidenced by reduced FAT and increased RDT. The cingulum bundle connects the limbic system with the prefrontal cortex. “Recurrent delusions, which are thought to be induced by an increase in limbic dopamine, [may] ultimately lead to a change in the structural integrity of the connections to and from the limbic system,” the authors wrote.

Additionally, increased free-water in the left cingulum bundle may indicate the presence of neuroinflammation or atrophy. Although neuroinflammation within the brain parenchyma has previously been implicated in the pathophysiology of schizophrenia, a recent PET imaging study found no evidence of increased microglial activation in the prefrontal cortex or hippocampus among medication free, or antipsychotic medication naive, patients.

Taken together, “potential treatments for delusions in schizophrenia could aim to both increase myelination and reduce neuroinflammation and atrophy in the cingulum bundle, which would require polypharmacy,” the authors concluded.

There has been a question of whether antipsychotic medications are truly acting upon "primary" negative symptoms, or whether they are instead improving "secondary" negative symptoms via improvement in positive or ...